During the first year of this grant I propose to develop a panel of monoclonal antibodies directed against the thyroid hormone receptor. In the following two years, I will use the monoclonal antibodies in two related, but mutually indrpendent studies: 1) purification of the thyroid hormone receptor by immunoaffinity chromatography, 2) identification by immunological techniques of a clone(s) of the thyroid hormone receptor cDNA using an expression vector system. The successful development of this project will represent a significant contribution to the field of thyroid hormone action and may lead to a better understanding of the mechanisms by which hormones regulate gene expression in health and disease. Dr. Herbert Samuels, my sponsor, has been my research advisor from the beginning of my medical school career when I first studied thyroid hormone action; he is keenly interested in developing this work. The facilities and personnel in Dr. Samuels' laboratory are outstanding and can well support the most sophisticated molecular biological techniques. Additionally, the Medical School Departments of Pharmacology and Biochemistry have agreed to cooperate and support our efforts in specific areas of this proposal. Throughout the entire period of my undergraduate, medical school, and postgraduate training I have pursued an intense interest in the molecular basis of metabolic control. This project will greatly extend my expertise in experimental design and technique in state-of-the-art methodologies. This award forms the bridge between my formal training and independent research.